title: Exogenous polyamines promote osteogenic differentiation by reciprocally regulating osteogenic and adipogenic gene expression.
abstract: Polyamines are naturally occurring organic polycations that are ubiquitous in all organisms, and are essential for cell proliferation and differentiation. Although polyamines are involved in various cellular processes, their roles in stem cell differentiation are relatively unexplored. In this study, we found that exogenous polyamines, putrescine, spermidine, and spermine, promoted osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) without inducing cell death or apoptosis. Alkaline phosphatase (ALP) activity and the mRNA level of osteogenic genes, including Runx2, ALP, osteopontin, and osteocalcin, were up-regulated by exogenous polyamines. When hBMSCs were cultured at high cell density favoring adipocyte formation, exogenous polyamines resulted in down-regulation of adipogenic genes such as PPARγ, aP2, and adipsin. Extracellular matrix mineralization, a marker for osteoblast maturation, was enhanced in the presence of exogenous polyamines, while lipid accumulation, an indication of adipogenic differentiation, was attenuated. Exogenous polyamines increased the mRNA expression of polyamine-modulated factor 1 (PMF-1) and its downstream effector, spermidine/spermine N(1)-acetyltransferase (SSAT), while that of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, was suppressed. These results lead to possible connections between polyamine metabolism and osteogenic differentiation pathways. To summarize, this study provides evidence for the involvement of polyamines in osteogenic differentiation of hBMSCs, and is the first to demonstrate that osteogenic and adipogenic differentiation are reciprocally regulated by exogenous polyamines.
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Mon-Juan
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuan-Pin
authors.initials: YP
authors.lastname: Huang
authors.forename: Yi-Chiang
authors.initials: YC
authors.lastname: Hsu
authors.forename: Lan-Hsin
authors.initials: LH
authors.lastname: Chiang
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Chen
authors.forename: Gwo-Jaw
authors.initials: GJ
authors.lastname: Wang
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*; D011700:Putrescine / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D013096:Spermine; D000469:Alkaline Phosphatase; D013095:Spermidine; D011700:Putrescine
keywords: ADIPOGENIC DIFFERENTIATION; MESENCHYMAL STEM CELLS; OSTEOGENIC DIFFERENTIATION; POLYAMINES